This proposal will test the hypothesis that kallikrein 6 (KLK6) protein is functionally involved in, and may be a useful marker of, colon carcinogenesis. We have shown that: 1) KLK6 protein can be detected at the adenomas in the mouse colon, and in human colon tumors; 2) KLK6 function blocking antibody attenuates invasion of colon cancer cells; and 3) colon cancer cells with knockdown of KLK6 do not form distant metastases in SCID mouse model and increase animal survival rates. To test the overall hypothesis, we propose the following specific aims: 1) determine the role of KLK6 in the colon cancer progression in vivo; 2) determine the role of KLK6 in colon cancer metastasis; 3) evaluate KLK6 protein expression and enzymatic activity in the colon. The major objectives of this proposal are to determine the role of KLK6 in colon tumor and metastasis formation, develop an imaging modality for measuring of KLK6 enzymatic activity in the colon and correlate it with disease progression.